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Biomedical subjects

W Rand

Publications and source records attributed to W Rand.

At least 19 recordsLinked to original sources
PubMed2002

Binge eating disorder in extreme obesity.

OBJECTIVE: To determine whether extremely obese binge eating disorder (BED) subjects (BED defined by the Eating Disorder Examination) differ from their extremely obese non-BED counterparts in terms of their eating disturbances, psychiatric morbidity and health status. DESIGN: Prospective clinical comparison of BED and non-BED subjects undergoing gastric bypass surgery (GBP). SUBJECTS: Thirty seven extremely obese (defined as BMI > or = 40 kg/m(2)) subjects (31 women, six men), aged 22-58 y. MEASUREMENTS: Eating Disorder Examination 12th Edition (EDE), Three Factor Eating Questionnaire (TFEQ), Structured Clinical Interview for the Diagnostic and Statistical Manual-IV (SCID-IV), Short-Form Health Status Survey (SF-36), and 24 h Feeding Paradigm. RESULTS: Twenty-five percent of subjects were classified as BED (11% met full and 14% partial BED criteria) and 75% of subjects were classified as non-BED. BED (full and partial) subjects had higher eating disturbance in terms of eating concern and shape concern (as found by the EDE), higher disinhibition (as found by the TFEQ), and they consumed more liquid meal during the 24 h feeding paradigm. No difference was found in psychiatric morbidity between BED and non-BED in terms of DSM-IV Axis I diagnosis. The health status scores of both BED and non-BED subjects were significantly lower than US norms on all subscales of the SF-36, particularly the BED group. CONCLUSION: Our findings support the validity of the category of BED within a population of extremely obese individuals before undergoing GBP. BED subjects differed from their non-BED counterparts in that they had a greater disturbance in eating attitudes and behavior, a poorer physical and mental health status, and a suggestion of impaired hunger/satiety control. However, in this population of extremely obese subjects, the stability of BED warrants further study.

Adult↗
PubMed2001

Cognitive therapy, nutritional therapy and their combination in the treatment of bulimia nervosa.

BACKGROUND: This study compared the effectiveness of cognitive therapy (CT), nutritional therapy (NT), the combination of cognitive and nutritional therapy (CNT), against a control condition of support group (SG) in the treatment of bulimia nervosa. METHODS: One hundred female out-patients who fulfilled DSM-III-R criteria for bulimia nervosa were randomized to the four treatment groups. NT and CT were designed to cover different areas with minimal overlap, and CNT provided all of the features of both of these treatments. The control condition was conducted in a group self-help format. Each of the treatments lasted 14 weeks. RESULTS: All three active treatments as well as SG produced significant decreases in binge/vomit episodes. Intent-to-treat analysis found CNT and CT to be significantly more effective than SG in retaining subjects in treatment and completion of study, as well as in producing greater improvements in dysfunctional attitudes and self-control. CNT was superior to SG in achieving abstinence from bulimic behaviour. NT was superior to SG only in increase of self-control. Logistic regression found that the cognitive component, whether given alone or in conjunction with NT, and higher pre-treatment self-control scores were significant predictors for both completion of study and abstinence. CONCLUSION: CT (either alone, or in combination with nutritional therapy) remains the treatment of choice for bulimia nervosa. A treatment escalation approach should be tested for the treatment of bulimia with the more intensive and less widely available CT (with or without nutritional counselling) offered after patients have failed the less intensive and more widely available support group treatment.

Adolescent↗
PubMed2001

Short-term comparative outcomes associated with the use of GP IIb/IIIa antagonists in patients undergoing coronary intervention.

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa antagonists reduce the occurrence of death, myocardial infarction (MI) and urgent revascularization among patients undergoing percutaneous coronary intervention (PCI). Despite a similar mechanism of platelet inhibition, the three currently approved agents vary widely in cost. PURPOSE: The purpose of this prospectively designed, retrospective analysis was to determine clinical outcomes for patients receiving abciximab, tirofiban or eptifibatide as adjunctive therapy during PCI at a single center. We hypothesized that there would be no difference in outcomes during hospitalization following PCI in patients receiving tirofiban or eptifibatide compared with those patients who received abciximab. Outcomes examined included in-hospital mortality, hemorrhagic procedural complications, need for recatheterization, peak creatine kinase following intervention and length of hospital stay (LOS). RESULTS: Two hundred and sixty seven consecutive patients in whom GP IIb/IIIa antagonist therapy was initiated in the catheterization laboratory for PCI were analyzed. Abciximab-treated patients were more likely to be undergoing primary (p<0.001) and rescue (p=0.022) PCI and to have received fibrinolytic therapy (p=0.013) when compared to patients receiving tirofiban or eptifibatide. There were no significant differences between abciximab- and non abciximab-treated patients in either the primary PCI or non primary PCI groups in any of the studied endpoints. In patients undergoing primary PCI, abciximab-treated patients when compared with non abciximab-treated patients exhibited a trend toward an increase in hospital LOS (7.8+/-7.0 d vs 6.2+/-3.9, p=0.19) and in the frequency of hemorrhagic complications (22.1% vs 5.3%, p=0.11). In patients not receiving fibrinolytic therapy, abciximab-treated patients experienced a trend toward increased hemorrhagic complications following PCI when compared to non abciximab-treated patients (10.2% vs 6.0%, p=0.28). Complications distant from the vascular access site comprised 62.5% of hemorrhagic complications in the abciximab-treated group, but only 20% of the complications in the non-abciximab treated population (p<0.001). These data suggest no differences in acute outcomes between groups of patients receiving abciximab or other approved GP IIb/IIIa antagonists highlighting a potential significant cost saving. These data will require interpretation following the publication of comparative trials.

Abciximab↗
PubMed2000

Effects of losartan and captopril on left ventricular volumes in elderly patients with heart failure: results of the ELITE ventricular function substudy.

BACKGROUND: The mechanism by which angiotensin-converting enzyme inhibitors reduce mortality rates and disease progression in patients with heart failure is likely mediated in part through prevention of adverse ventricular remodeling. This study examined the effects of the angiotensin-converting enzyme inhibitor captopril and the angiotensin II type 1 receptor antagonist losartan on ventricular volumes and function in elderly patients with heart failure and reduced left ventricular ejection fraction (< or =40%). METHODS: Patients underwent radionuclide ventriculograms (RVG) at baseline and were randomized to either captopril (n = 16) or losartan (n = 13). After 48 weeks, another RVG was obtained. Therapy was then withdrawn for at least 5 days, and the RVG was repeated while the patient was not receiving the drug. RESULTS: At 48 weeks both captopril and losartan significantly reduced left ventricular (LV) end-diastolic volume index (135 +/- 26 to 128 +/- 23 mL/m(2) for losartan, P <.05 vs baseline; 142 +/- 25 to 131 +/- 20 mL/m(2) for captopril, P <.01; mean (SD). Captopril also reduced LV end-systolic volume index (98 +/- 24 to 89 +/- 21 mL/m(2), P <.01 vs. baseline), whereas a nonsignificant trend was observed for the losartan group (97 +/- 23 to 90 +/- 16 mL/m(2), P = not significant). The between-group differences in the changes in LV volumes were not statistically significant. After drug withdrawal, LV end-diastolic volume index remained significantly lower than baseline in the captopril group (P <.01). CONCLUSIONS: Both captopril and losartan prevent LV dilation, representing adverse ventricular remodeling, previously seen with placebo treatment. Reverse remodeling was observed in the captopril group. On the basis of these results, the relative effects on LV remodeling do not provide a rationale for a survival benefit of losartan over captopril.

Aged↗
PubMed2000

Concentrations of substance P and prostaglandin E2 in synovial fluid of normal and abnormal joints of horses.

OBJECTIVE: To correlate substance P content of synovial fluid with prostaglandin E2 content, radiographic evidence of joint abnormality, and anatomic location of the joint for normal and osteoarthritic joints of horses. SAMPLE POPULATION: Synovial fluid from 46 normal joints in 21 horses and 16 osteoarthritic joints in 10 horses. PROCEDURE: Normal and osteoarthritic joints were identified by clinical and radiographic examination, by response to nerve blocks, during scintigraphy or surgery, or by clinicopathologic evaluation. Substance P and prostaglandin E2 contents of synovial fluid were determined by radioimmunoassay. Radio-graphs of joints were assigned a numeric score reflecting severity of lesions. Joints were assigned a numeric score reflecting anatomic location. RESULTS: Median concentrations of substance P and prostaglandin E2 were significantly increased in osteoarthritic joints, compared with normal joints. A significant correlation was found between concentrations of substance P and prostaglandin E2 in synovial fluid, but a correlation was not detected between substance P concentration in synovial fluid and anatomic location of the joint or between radiographic scores of osteoarthritic joints and concentrations of substance P or prostaglandin E2. CONCLUSIONS AND CLINICAL RELEVANCE: A correlation existed between concentrations of substance P and prostaglandin E2 in synovial fluid obtained from normal and osteoarthritic joints. However, content of substance P in synovial fluid cannot be predicted by the radiographic appearance of the joint or its anatomic location. Substance P and prostaglandin E2 may share an important and related role in the etiopathogenesis of osteoarthritis, lending credence to the importance of neurogenic inflammation in horses.

Animals↗
PubMed1999

Central nervous system manifestations of childhood shigellosis: prevalence, risk factors, and outcome.

BACKGROUND AND OBJECTIVE: Alterations in consciousness, including seizures, delirium, and coma, are known to occur during Shigella infection. Previous reports have suggested that febrile convulsions and altered consciousness are more common during shigellosis than with other childhood infections. Those reports, however, have been from locations where S dysenteriae type 1 was not common, thus making it difficult to assess the specific contribution that S dysenteriae type 1 infection, and Shiga toxin, might make to the pathogenesis of altered consciousness in children with shigellosis. In this study we seek to determine the prevalence, risk factors, and outcome of altered consciousness in children with shigellosis in Bangladesh, a country where infection with all four species of Shigella is common. We particularly focus on the importance of metabolic abnormalities, which we have previously shown to be a common feature of shigellosis in this population. METHODS: This study was conducted at the Diarrhea Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh in Dhaka, Bangladesh, which provides care free of charge to persons with diarrhea. During 1 year, a study physician identified all inpatients infected with Shigella by checking the logs of the Clinical Microbiology Laboratory daily. Study physicians obtained demographic and historical information by reviewing the patient charts and by interviewing patients, or their parents or guardians, to confirm or complete the history of illness obtained on admission. Patients were categorized as being conscious or unconscious based on a clinical scale; having a seizure documented in the hospital; or having a seizure by history during the current illness that was not witnessed by medical personnel. Patient outcome was classified as discharged improved, discharged against medical advice, transferred to another health facility, or died in the Treatment Centre. Laboratory examinations were ordered at the discretion of the attending physician; all such information was recorded on the study form. Clinical management was by the attending physician. Factors independently predictive of a documented seizure, or of unconsciousness, were determined using a multiple logistic regression analysis. For this analysis variables associated with unconsciousness or a documented seizure in the analysis of variance or chi2 analyses were entered into the regression equation and eliminated in a backward stepwise fashion if the probability associated with the likelihood ratio statistic exceeded .10. RESULTS: During this 1-year study, 83 402 persons with diarrhea came to the Treatment Centre for care, and 6290 patients were admitted to the inpatient unit. Shigella was isolated from a stool or rectal swab sample of 863 (13.7%) of the inpatients. Seventy-one (8%) of the inpatients with shigellosis were >/=15 years old; 61 (86%) were conscious; 10 (14%) were unconscious; none had either a documented seizure or a seizure by history during this illness. Seven hundred ninety-two patients were <15 years old (92%); 654 (83%) were conscious; 73 (9%) were unconscious; 41 (5%) had a documented seizure (compared with >/=15-year age group); 24 (3%) had a seizure by history during this illness. Of the 41 patients with documented seizures, 19 (46.3%) had a seizure at the time of admission, and 22 (53.7%) had a seizure after admission. Twenty-five (61.0%) of the 41 patients with documented seizures were reported to have a seizure during this illness before coming to the Treatment Centre. Clinical features that are known to cause altered consciousness-fever, severe dehydration, hypoglycemia, hyponatremia, or meningitis-were present in 38 (92.7%) of the 41 patients in whom a seizure was witnessed and in 67 (91.8%) of the 73 patients who were unconscious. Nineteen (46. 3%) of the patients who had a seizure documented had two of these five features, 4 (9.8%) had three, and 1 (2. (ABSTRACT TRUNCATED)

Adolescent↗
PubMed1998

Preliminary outcomes following cryosurgical ablation of the prostate in patients with clinically localized prostate carcinoma.

PURPOSE: Cryosurgical ablation of the prostate is a novel therapeutic modality that induces cell lysis in the prostate by direct application of low temperatures. We have been conducting an ongoing prospective pilot study of the use of cryosurgical prostate ablation in treating patients with nonmetastatic prostate adenocarcinoma since January 1993. Results in 145 consecutive patients with mean 36 months and minimum 12 months of followup are presented. MATERIALS AND METHODS: Accrual was open to patients with clinical stages T1a to T3c prostate adenocarcinoma. Pelvic lymph node dissections were recommended but not required for patients with prostate specific antigen (PSA) greater than 15 ng./ml. before study entry. PSA changes, random prostate biopsy findings and morbidities after cryosurgical prostate ablation were recorded for each patient. RESULTS: Overall actuarial rates at 42 months for maintaining PSA less than 0.3 and less than 1.0 were 59% and 66%, respectively. The overall actuarial progression-free rate at 60 months was 56%. Among 160 biopsies performed 16% showed some evidence of residual carcinoma. Overall crude rates of maintaining either a negative biopsy or PSA less than 0.3 at 6 and 24 months after cryosurgical prostate ablation were 87% and 73%, respectively. Significantly higher morbidities were seen in previously radiated patients undergoing cryosurgical prostate ablation compared to those with no prior radiation. Among nonradiated patients 85% experienced no significant morbidity after cryosurgical prostate ablation. CONCLUSIONS: Although preliminary, short-term outcomes after cryosurgical prostate ablation appear to be comparable to identical outcomes reported for external beam radiotherapy. Based on these results cryosurgical prostate ablation appears to be an effective therapeutic alternative for treating patients with localized prostate adenocarcinoma.

Actuarial Analysis↗
PubMed1998

A two-part phase I trial of high-dose interleukin 2 in combination with soluble (Chinese hamster ovary) interleukin 1 receptor.

Our purpose was to determine the maximum tolerated dose and toxicity associated with soluble Chinese hamster ovary [s(CHO)] recombinant human interleukin (IL) 1 receptor (IL-1R; Immunex, Seattle, WA) administration in humans and to determine the effective biological dose and/or maximum tolerated dose of the s(CHO) IL-1R in combination with high-dose IL-2 as determined by reduction in IL-2 toxicity and modulation of its biological effects. Twenty-seven patients with metastatic cancer were treated with escalating doses of s(CHO) IL-1R at 1, 1, 5, 10, 20, 40, and 55 mg/m2 i.v. on days -6 (except cohort 2), 1, and 15 and IL-2 at doses of 300,000 IU/kg (cohort 1) and 600,000 IU/kg (cohorts 2-7) i.v. every 8 h on days 1-5 and 15-19. No toxicity directly attributable to s(CHO) IL-1R was observed. The median number of IL-2 doses was 23. Hypotension and neurotoxicity were the major dose-limiting toxicities for the IL-2/s(CHO) IL-1R combination. Of the 24 patients treated with full-dose IL-2, there were six responses, three complete and three partial (response rate, 25%). Three patients developed thyroid dysfunction, and all 3 responding melanoma patients exhibited vitiligo. The t1/2 of s(CHO) IL-1R alone was 24-30 h and was not significantly altered by coadministration with IL-2. Whole-blood functional assays indicated that sufficient s(CHO) IL-1R was present in the circulation at top dose levels to inhibit the in vitro effects of IL-1beta on IL-8 induction; however, no effect on IL-2-induced IL-8 induction, or on the IL-1beta- or IL-2-induced tumor necrosis factor production, was observed. Suppression of IL-2-mediated tumor necrosis factor alpha and IL-6 induction in vivo during the first 24 h after IL-2 administration was observed, and the neutrophil chemotactic defect normally seen with IL-2 was not observed. IL-1R antagonist induction far exceeded that seen previously with IL-2 alone. No inhibition of either serum C-reactive protein induction or enhanced urinary nitrate excretion and no consistent effect on IL-2-related changes in peripheral blood mononuclear cell phenotype or endothelial adhesion molecule expression were seen. The coadministration of s(CHO) IL-1R produced no apparent reduction in IL-2 clinical toxicity manifested by either the ability to administer more IL-2 than anticipated or a reduction in the toxicity associated with a given amount of IL-2. Therefore, no effective biological dose could be identified for the s(CHO) IL-1R.

Adult↗
PubMed1997

Orbital color Doppler imaging in carotid occlusive disease.

OBJECTIVE: To define orbital circulation abnormalities identified by color Doppler imaging in patients with severe carotid occlusive disease. PATIENTS: Twenty-four patients referred to a hospital-based neuro-ophthalmology service with hemodynamically significant carotid occlusive disease (> 75% stenosis) were prospectively studied. Eight had signs of ocular ischemic syndrome; 12 of the 24 patients underwent endarterectomy. MAIN OUTCOME MEASURES: Peak systolic velocity of the central retinal, posterior ciliary, and ophthalmic artery and pulsatility indexes as determined by color Doppler imaging. METHODS: Color Doppler imaging was performed using a 7.5-MHz probe. Both eyes were studied in all patients and carotid duplex imaging was obtained. RESULTS: All patients with hemodynamically significant carotid occlusive disease had lower mean peak systolic velocities in the central retinal, posterior ciliary, and ophthalmic arteries and higher pulsatility indexes compared with normal control patients. Endarterectomy improved peak systolic velocities. Reversal of ophthalmic flow direction as a separate variable was unassociated with altered mean central retinal or posterior ciliary artery flow velocities. Patients with ocular ischemic syndrome may have similar orbital color Doppler imaging findings compared with patients with severe carotid occlusive disease without overt manifestations of chronic ocular ischemia. CONCLUSION: Orbital circulation is highly adaptable even when faced with severe compromise in proximal blood flow.

Adult↗
PubMed1997

Randomized placebo-controlled clinical trial of high-dose interleukin-2 in combination with a soluble p75 tumor necrosis factor receptor immunoglobulin G chimera in patients with advanced melanoma and renal cell carcinoma.

PURPOSE: A randomized, double-blind, placebo-controlled trial was performed to compare the toxicity and biologic effects of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus the recombinant human soluble p75 tumor necrosis factor (TNF) receptor immunoglobulin G (IgG) chimera (rhuTNFR:Fc) with high-dose IL-2 alone in patients with advanced melanoma and renal cell carcinoma. PATIENTS AND METHODS: Twenty patients with advanced melanoma or renal cell carcinoma were randomized to receive IL-2 (Chiron, Emeryville, CA) 600,000 IU/kg every 8 hours on days 1 to 5 and 15 to 19 (maximum, 28 doses) combined with placebo or the rhuTNFR:Fc fusion protein (Immunex, Seattle, WA) 10 mg/m2 on days 1 and 15 and 5 mg/m2 on days 3, 5, 17, and 19. The impact of rhuTNFR:Fc on IL-2 toxicity and biologic effects was evaluated. RESULTS: No clinically significant difference in toxicity was observed in the two treatment arms. The adjusted median number of IL-2 doses administered during cycle 1 was 24.5 (range, seven to 28) and 21.5 (range, five to 27) for the placebo and rhuTNFR:Fc arms, respectively (P = .544). IL-2-induced TNF bioactivity, neutrophil chemotactic defect, and serum IL-6, IL-8, and IL-1 receptor antagonist (IL-1RA) induction were suppressed by rhuTNFR:Fc. Two of nine assessable patients (22%) on IL-2/placebo and three of 10 patients (30%) on IL-2/rhuTNFR:Fc responded. CONCLUSION: Despite evidence of in vitro neutralization of TNF functional activity and partial inhibition of other secondary biologic effects of IL-2, rhuTNFR:Fc does not reduce the clinical toxicity associated with high-dose IL-2 therapy. These results suggest that the toxicity and antitumor effects of IL-2 treatment are independent of circulating TNF.

Adult↗
PubMed1997

Increased serum total creatine kinase and creatine kinase isoenzyme MB after cryosurgical ablation of the prostate.

PURPOSE: Several reports have documented that the MB isoenzyme of creatine kinase is present in prostatic tissue. However, since it has been shown that lower urinary tract manipulations, including transurethral prostatectomy, do not significantly increase serum creatine kinase isoenzyme MB levels, such elevations, which are found in patients after prostatic surgery, are believed to be specific for myocardial infarction. We examined whether cryosurgical ablation of the prostate altered serum creatine kinase or isoenzyme MB levels. MATERIALS AND METHODS: In 81 consecutive patients undergoing routine cryosurgical ablation of the prostate serum levels of creatine kinase and creatine kinase isoenzyme MB were measured from peripheral blood specimens drawn preoperatively, in the recovery room and at 8 and 24 hours postoperatively. Postoperative electrocardiograms were compared to the preoperative study. RESULTS: In 72 of 81 patients (89%) significant elevations in creatine kinase and creatine kinase isoenzyme MB levels were noted at all time points after cryosurgical ablation of the prostate and appeared to reach a peak at 16 hours postoperatively. The mean increases within the first 8 hours after cryosurgical ablation of the prostate were 1,355 units per 1. for creatine kinase and 46.6 ng./ml. for creatine kinase isoenzyme MB. No patient had any significant changes on the postoperative electrocardiogram. All 9 patients (11%) who did not have significant creatine kinase or creatine kinase isoenzyme MB levels after cryosurgery had undergone prior cryosurgery or combined radiation and hormonal therapy. CONCLUSIONS: Cryosurgical ablation of the prostate appears to produce elevations in serum creatine kinase and creatine kinase isoenzyme MB, which are specific to the procedure. Assays for creatine kinase isoenzyme MB are unreliable to render a diagnosis of myocardial infarction after cryosurgical ablation of the prostate.

Adenocarcinoma↗
PubMed1996

Use of fluoxetine to treat dominance aggression in dogs.

OBJECTIVE: To evaluate fluoxetine for the treatment of owner-directed dominance aggression in dogs. DESIGN: Prospective study. ANIMALS: 9 dogs of various breeds, ages, and either sex determined to have owner-directed dominance aggression. PROCEDURE: Placebo and fluoxetine (1 mg/kg of body weight) were compared for the treatment of owner-directed dominance aggression in a single-blind crossover study. Owners were instructed to record aggressive and nonaggressive responses of their dogs daily on a canine-overt aggression chart for the 5-week duration of the study. Total aggression scores (linear and geometric) were calculated for each week of the study. The frequency of individual responses was also analyzed independently. RESULTS: Fluoxetine resulted in a significant (P = 0.01) reduction in owner-directed dominance aggression after 3 weeks of treatment. No particular aggressive response accounted for the overall reduction in aggression. CLINICAL IMPLICATIONS: Fluoxetine may be useful in the management of dominance aggression in dogs.

Aggression↗
PubMed1996

Effect of dietary protein content on behavior in dogs.

OBJECTIVE: To determine the effect that feeding diets containing a low (17%), medium (25%), or high (32%) protein content would have on behavior in dogs. DESIGN: Prospective, controlled study. ANIMALS: 12 dogs with dominance aggression, 12 dogs with hyperactivity, 12 dogs with territorial aggression, and 14 control dogs without behavioral problems. PROCEDURE: Dogs were fed each of the diets for a 2-week period, and owners were instructed to score their dogs' behavior on a daily basis. RESULTS: Behavior of the dogs with dominance aggression, dogs with hyperactivity, and control dogs was unchanged by the dietary manipulations. Territorial aggression was significantly reduced when dogs were fed the low- or medium-protein diet, compared with territorial aggression when fed the high-protein diet. Post hoc analysis indicated that this effect was attributable to a marked reduction in aggression in a subset of the group (n = 7) in which territorial aggression was a result of fear. CLINICAL IMPLICATIONS: Results of this study suggest that a reduction in dietary protein content is not generally useful in the treatment of behavior problems in dogs, but may be appropriate in dogs with territorial aggression that is a result of fear.

Aggression↗
PubMed1996

Open vs endoscopic carpal tunnel release.

We examined a consecutive group of patients who had undergone either open (34 patients) or single portal endoscopic (12 patients) carpal tunnel release performed by one surgeon over a period of 3 years. Fifty-seven total procedures were performed. There were no operative complications. Retrospective evaluation was done by questionnaire. We were unable to demonstrate any statistically significant difference between the two groups in terms of return to work, return to activities of daily living, or on a symptom severity scale.

Activities of Daily Living↗
PubMed1995

Evaluation of a two-phase scid mouse model preconditioned with anti-interferon-gamma monoclonal antibody for drug testing against Cryptosporidium parvum.

One 1-mg injection of anti-interferon-gamma monoclonal antibody (anti-IFN-gamma MAb) into newly weaned scid mice 2 h before challenge with Cryptosporidium parvum oocysts markedly exacerbated the course of the infection for > or = 47 days, compared with challenged mice that received an equivalent dose of irrelevant MAb. Oocyst excretion in feces started 4-6 days after challenge and continued at high levels for > or = 47 days. Loss of body weight was also apparent. The extent and distribution of mucosal infection were profound, involving the stomach and several segments of the small and large intestines. The acute phase, which involved infection of the gut, was during the first 25 days after challenge. The following chronic phase consistently involved, in addition, infection of the hepatobiliary tract. The acute phase is a useful model in which to test luminally active drugs, while the chronic phase may be used in the future to test drugs that are active against hepatobiliary tract infections as well.

Amebicides↗
PubMed1994

Equine self-mutilation syndrome (57 cases)

Owners who believed they had a horse with self-mutilating behavior were asked to complete a questionnaire to obtain information on the signalment, clinical history, clinical signs, management, and treatment of the condition. Fifty-two owners of 59 horses responded; 2 cases were omitted because an organic cause was determined. Owners also were asked to complete information for unaffected horses on the same farm. Various breeds were affected, and of the 57 horses, 20 were stallions, 31 were geldings, and 6 were mares. Affected horses tended to develop the condition prior to sexual maturity. Clinical signs included glancing or biting at the flank or pectoral areas, bucking, kicking, vocalizing, rubbing, spinning, or rolling. Several management and environmental factors were examined, but none were found to be exclusively related to expression of the disorder. Castration was associated with improvement in 7 of 10 stallions. Medications and changes in management reduced or prevented the behavior in some horses. The syndrome appears to be similar to Tourette's syndrome of human beings.

Age Factors↗
PubMed1994

Evaluation of an animal model system for cryptosporidiosis: therapeutic efficacy of paromomycin and hyperimmune bovine colostrum-immunoglobulin.

Several immunodeficient rodent models currently exist in which persistent, largely asymptomatic, Cryptosporidium parvum infections can be established. Piglets, in contrast, develop a self-limiting diarrheal illness. We have consequently developed an animal model system in which scid mice were used to screen drugs for inhibitory activity against C. parvum, after which the drugs' therapeutic potential was evaluated with piglets. Paromomycin and hyperimmune bovine colostrum-immunoglobulin were selected to evaluate this system. C. paravum infections in suckling scid mice tended to be associated with villus surfaces, while in weaned and in older scid mice infections were more commonly localized in abscessed crypts. Rates of oocyst shedding in suckling scid mice were 50 to 200 times higher than in weaned mice and therefore made suckling mice a considerably more sensitive model for drug testing. Paromomycin given in high doses over 9 to 10 days was not toxic to either scid mice (3,000 mg/kg of body weight per day) or piglets (500 mg/kg/day). Paromomycin treatment was very effective against villus surface infections in suckling mice and considerably less effective against infections in inaccessible sites such as abscessed crypts and stomach pits seen in weaned and adult scid mice. The therapeutic efficacy of paromomycin in piglets depended on the severity of the diarrheal illness. Mild to moderate diarrhea and infection were cleared after paromomycin treatment of piglets infected with one C. parvum isolate. However, paromomycin had no impact on severely affected piglets infected with a second isolate, presumably because of a rapid transit time through the gut. In contrast to paromomycin hyperimmune bovine colostrum-immunoglobulin treatment reduced the rate of C. parvum infection moderately in scid mice and only slightly in piglets, again probably because of a rapid transit time through the gut and inactivation in the stomach. It was also clear that the impact of effective drugs against C. parvum can be detected within 5 days after the onset of treatment in either model.

Animals↗